Trial Outcomes & Findings for Safety and Efficacy Study of LUM001 in the Treatment of Cholestatic Liver Disease in Patients With Alagille Syndrome (NCT NCT01903460)
NCT ID: NCT01903460
Last Updated: 2019-03-28
Results Overview
Participants were required to fast for at least 4 hours; only water was permitted prior to collection. A negative change from baseline indicates that the level of bile acid decreased.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Baseline to 13 weeks or end of treatment
Results posted on
2019-03-28
Participant Flow
Participant milestones
| Measure |
LUM001 140ug/kg/Day
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
LUM001 280ug/kg/Day
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
Placebo Cohort A
Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment.
|
Placebo Cohort B
Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
8
|
3
|
3
|
|
Overall Study
COMPLETED
|
6
|
8
|
3
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
LUM001 140ug/kg/Day
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
LUM001 280ug/kg/Day
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
Placebo Cohort A
Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment.
|
Placebo Cohort B
Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Safety and Efficacy Study of LUM001 in the Treatment of Cholestatic Liver Disease in Patients With Alagille Syndrome
Baseline characteristics by cohort
| Measure |
LUM001 140ug/kg/Day
n=6 Participants
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
LUM001 280ug/kg/Day
n=8 Participants
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
Placebo Cohort A
n=3 Participants
Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment.
|
Placebo Cohort B
n=3 Participants
Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
5.8 years
STANDARD_DEVIATION 4.49 • n=5 Participants
|
6.8 years
STANDARD_DEVIATION 6.73 • n=7 Participants
|
5.0 years
STANDARD_DEVIATION 2.00 • n=5 Participants
|
4.3 years
STANDARD_DEVIATION 3.21 • n=4 Participants
|
5.9 years
STANDARD_DEVIATION 4.93 • n=21 Participants
|
|
Age, Customized
< 2 years
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
3 participants
n=21 Participants
|
|
Age, Customized
2 to 4 years
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
7 participants
n=21 Participants
|
|
Age, Customized
5 to 8 years
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
5 participants
n=21 Participants
|
|
Age, Customized
9 to 12 years
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
2 participants
n=21 Participants
|
|
Age, Customized
13 to 18 years
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
3 participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Region of Enrollment
United Kingdom
|
6 participants
n=5 Participants
|
8 participants
n=7 Participants
|
3 participants
n=5 Participants
|
3 participants
n=4 Participants
|
20 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline to 13 weeks or end of treatmentPopulation: The modified Intent-to-Treat (mITT) population, defined as all participants in the Safety population who had at least 1 post-baseline efficacy assessment. The Safety population was defined as all participants who were randomly assigned to study treatment and who received any amount of study drug.
Participants were required to fast for at least 4 hours; only water was permitted prior to collection. A negative change from baseline indicates that the level of bile acid decreased.
Outcome measures
| Measure |
LUM001 140ug/kg/Day
n=6 Participants
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
LUM001 280ug/kg/Day
n=8 Participants
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
LUM001 Overall
n=14 Participants
Participants received either dose of LUM001 for up to 10 or 13 weeks, then were followed for 4 weeks after treatment.
|
Placebo Overall
n=6 Participants
Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment.
|
|---|---|---|---|---|
|
Change From Baseline to Week 13 (End of Treatment) in Fasting Serum Bile Acid Level
|
-82.864 umol/L
Standard Error 50.1513
|
-49.388 umol/L
Standard Error 43.4732
|
-66.126 umol/L
Standard Error 33.1208
|
-42.157 umol/L
Standard Error 50.0903
|
SECONDARY outcome
Timeframe: Baseline to 13 weeks or end of treatmentPopulation: The mITT population, defined as all participants in the Safety population who had at least 1 post-baseline efficacy assessment. The Safety population was defined as all participants who were randomly assigned to study treatment and who received any amount of study drug.
Analysis of liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A negative change from baseline indicates that the level of that enzyme decreased.
Outcome measures
| Measure |
LUM001 140ug/kg/Day
n=6 Participants
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
LUM001 280ug/kg/Day
n=8 Participants
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
LUM001 Overall
n=14 Participants
Participants received either dose of LUM001 for up to 10 or 13 weeks, then were followed for 4 weeks after treatment.
|
Placebo Overall
n=6 Participants
Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment.
|
|---|---|---|---|---|
|
Change From Baseline to Week 13 (End of Treatment) in Liver Enzymes
ALT
|
59.3 U/L
Standard Error 20.99
|
10.5 U/L
Standard Error 18.06
|
34.9 U/L
Standard Error 13.86
|
2.7 U/L
Standard Error 21.06
|
|
Change From Baseline to Week 13 (End of Treatment) in Liver Enzymes
AST
|
37.2 U/L
Standard Error 13.64
|
-2.7 U/L
Standard Error 11.70
|
17.3 U/L
Standard Error 8.98
|
13.2 U/L
Standard Error 13.63
|
|
Change From Baseline to Week 13 (End of Treatment) in Liver Enzymes
ALP
|
71.4 U/L
Standard Error 53.35
|
31.6 U/L
Standard Error 43.59
|
51.5 U/L
Standard Error 36.13
|
19.7 U/L
Standard Error 60.76
|
SECONDARY outcome
Timeframe: Baseline to 13 weeks or end of treatmentPopulation: The mITT population, defined as all participants in the Safety population who had at least 1 post-baseline efficacy assessment. The Safety population was defined as all participants who were randomly assigned to study treatment and who received any amount of study drug.
The ItchRO was administered as a twice daily electronic diary (eDiary). Children ≥9 years of age completed the patient ItchRO; those between the ages of 5 and 8 completed the patient ItchRO with the assistance of their caregiver. There was no patient report for subjects under the age of 5. ItchRO scores range from 0 to 4, with the higher score indicating increasing itch severity. ItchRO average daily scores were calculated as the sum of daily scores (ie, the maximum of morning and evening scores) divided by the number of days. The average daily score was calculated by using the 7 days pre-treatment for baseline, and the last 7 days of treatment for Week 13. A negative change from Baseline indicates that itch severity decreased.
Outcome measures
| Measure |
LUM001 140ug/kg/Day
n=6 Participants
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
LUM001 280ug/kg/Day
n=8 Participants
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
LUM001 Overall
n=14 Participants
Participants received either dose of LUM001 for up to 10 or 13 weeks, then were followed for 4 weeks after treatment.
|
Placebo Overall
n=6 Participants
Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment.
|
|---|---|---|---|---|
|
Change From Baseline to Week 13 (End of Treatment) in Pruritus as Measured by The Patient And Observer Itch Reported Outcome (ItchRO) Average Daily Scores
Patient ItchRO
|
-1.159 units on a scale
Standard Error 0.5396
|
-0.608 units on a scale
Standard Error 0.4399
|
-0.883 units on a scale
Standard Error 0.3484
|
-0.811 units on a scale
Standard Error 0.5684
|
|
Change From Baseline to Week 13 (End of Treatment) in Pruritus as Measured by The Patient And Observer Itch Reported Outcome (ItchRO) Average Daily Scores
Observer ItchRO
|
-0.802 units on a scale
Standard Error 0.2732
|
-0.419 units on a scale
Standard Error 0.2318
|
-0.610 units on a scale
Standard Error 0.1776
|
-0.592 units on a scale
Standard Error 0.2690
|
Adverse Events
LUM001 140ug/kg/Day
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
LUM001 280ug/kg/Day
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo Overall
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LUM001 140ug/kg/Day
n=6 participants at risk
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
LUM001 280ug/kg/Day
n=8 participants at risk
Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment.
|
Placebo Overall
n=6 participants at risk
Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment.
|
|---|---|---|---|
|
Cardiac disorders
Bradycardia
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Deafness unilateral
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Ear pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Middle ear inflammation
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/6
|
12.5%
1/8 • Number of events 3
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
1/6 • Number of events 1
|
62.5%
5/8 • Number of events 8
|
16.7%
1/6 • Number of events 5
|
|
Gastrointestinal disorders
Abdominal pain lower
|
16.7%
1/6 • Number of events 2
|
0.00%
0/8
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain upper
|
16.7%
1/6 • Number of events 4
|
0.00%
0/8
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
66.7%
4/6 • Number of events 5
|
62.5%
5/8 • Number of events 9
|
33.3%
2/6 • Number of events 3
|
|
Gastrointestinal disorders
Frequent bowel movements
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
16.7%
1/6 • Number of events 2
|
0.00%
0/8
|
0.00%
0/6
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Gastrointestinal disorders
Toothache
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
25.0%
2/8 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Crying
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Feeling abnormal
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
|
General disorders
Malaise
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Pyrexia
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Infections and infestations
Ear infection
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
|
Infections and infestations
Nasopharyngitis
|
33.3%
2/6 • Number of events 2
|
12.5%
1/8 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
50.0%
3/6 • Number of events 5
|
12.5%
1/8 • Number of events 2
|
50.0%
3/6 • Number of events 6
|
|
Infections and infestations
Viral rash
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Anal injury
|
0.00%
0/6
|
25.0%
2/8 • Number of events 3
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Contusion
|
16.7%
1/6 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Investigations
Body temperature increased
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Vitamin E deficiency
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
16.7%
1/6 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
33.3%
2/6 • Number of events 2
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Hypoaesthesia
|
16.7%
1/6 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Somnolence
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Psychiatric disorders
Abnormal behaviour
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
1/6 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash generalised
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually
- Publication restrictions are in place
Restriction type: OTHER